Dataset Information

Quantitative proteomics of cryptococcal meningitis brain tissues

ABSTRACT: Quantitative proteomics of cryptococcal meningitis brain tissues and control brain tissues was carried out to study the host factors that are activated and differentially regulated in response to infection. Proteins isolated from infected brain tissues were subjected to trypsin digestion and then labeled using 4-plex iTRAQ labels. iTRAQ labeled peptides were subjected to fractionation by SCX. All the fractions were analyzed on the high resolution Orbitrap Velos mass spectrometer.

INSTRUMENT(S): LTQ Orbitrap Velos

ORGANISM(S): Homo Sapiens (human)

SUBMITTER: Akhilesh Pandey

PROVIDER: PXD000458 | Pride | 2015-07-22

REPOSITORIES: Pride

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Dataset's files

Source:

			Action	DRS
	CM_BrainTissues_iTRAQ.prot.prot.xml	Xml
	CM_brainTissue_iTRAQ.pep.pep.xml	Pepxml
	Crypto_Meningitis_iTRAQ_01.raw	Raw
	Crypto_Meningitis_iTRAQ_01_1_121004182539.raw	Raw
	Crypto_Meningitis_iTRAQ_02.raw	Raw

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Publications

Characterization of host response to Cryptococcus neoformans through quantitative proteomic analysis of cryptococcal meningitis co-infected with HIV.

Selvan Lakshmi Dhevi N LD Sreenivasamurthy Sreelakshmi K SK Kumar Satwant S Yelamanchi Soujanya D SD Madugundu Anil K AK Anil Abhijith K AK Renuse Santosh S Nair Bipin G BG Gowda Harsha H Mathur Premendu P PP Satishchandra Parthasarathy P Shankar S K SK Mahadevan Anita A Keshava Prasad T S TS

Molecular bioSystems 20150901 9

Cryptococcal meningitis is the most common opportunistic fungal infection causing morbidity and mortality (>60%) in HIV-associated immunocompromised individuals caused by Cryptococcus neoformans. Molecular mechanisms of cryptococcal infection in brain have been studied using experimental animal models and cell lines. There are limited studies for the molecular understanding of cryptococcal meningitis in human brain. The proteins involved in the process of invasion and infection in human brain st ...[more]

PMID: 26181685

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Project description:Meningitis is a life-threatening condition characterized by the inflammation of the leptomeningeal membranes surrounding the brain and spinal cord. The term meningitis is an umbrella term and includes several different etiologies. The majorities of meningitis cases are caused by viruses (viral meningitis; VM) and are often associated with low mortality rates and low risk of developing neurological. In contrast, meningitis caused by some viral infections, such as tick-borne encephalitis (TBE), can be life-threatening when left untreated with increased risk of developing neurological sequelae. Acute bacterial meningitis (ABM), however, is one of the leading causes of death due to infectious diseases worldwide and is associated with rapid disease progression, high mortality rates and increased risk of long-term neurological sequelae in survivors. As meningitis is caused by numerous different pathogens, the host-response is typically highly variable and it is currently unknown if different pathogens can introduce specific proteome changes in the cerebrospinal fluid (CSF). In this study we applied DIA-MS to provide novel insights for in-depth understanding of central nervous system functioning and host response during meningitis in a cohort of patients with differential diagnosis of meningitis, to account for variability contributed by different disease-causing pathogens. The results reveal drastic changes in the CSF proteome during meningitis, where in particular a massive increase of neutrophil derived proteins in the CSF correlated with ABM, suggesting that activated neutrophils play a particular role in ABM. Additionally both ABM and VM result in marked reduction of brain-specific proteins in the CSF, which could be indicative of pathophysiological mechanisms leading to brain damage. Furthermore, generation of lasso regression model enables separation of ABM with high sensitivity and specificity, demonstrating that several proteins are required to confidently discriminate between ABM, VM and BM.